Towards respiratory muscle-protective mechanical ventilation in the critically ill: technology to monitor and assist physiology

Inadequate delivery of ventilatory assist and unphysiological respiratory drive may severely worsen respiratory muscle function in mechanically ventilated critically ill patients. Diaphragm weakness in these patients is exceedingly common (>60% of patients) and associated with poor clinical outcomes, including difficult ventilator liberation, increased risks of intensive care unit (ICU) and hospital readmission, and mortality. The underlying mechanisms of diaphragm dysfunction were extensively discussed in this thesis. Pathways primarily include the development of diaphragm disuse atrophy due to muscle inactivity or low respiratory drive (strong clinical evidence), and diaphragm injury as a result of excessive breathing effort due to insufficient ventilator assist or excessive respiratory drive (moderate evidence, mostly from experimental work). Excessive breathing effort may also worsen lung injury through pathways that include high lung stress and strain, pendelluft, increased lung perfusion, and patient-ventilator dyssynchrony. Relatively little attention has been paid to the effects of critical illness and mechanical ventilation on the expiratory muscles; however, dysfunction of these muscles has been linked to inadequate central airway clearance and extubation failure. The motivation for performing the work presented in this thesis was the hypothesis that maintaining physiological levels of respiratory muscle activity under mechanical ventilation could prevent or attenuate the development respiratory muscle weakness, and hence, improve patient outcomes. This strategy, integrated with lung-protective ventilation, was recently proposed by international experts from different professional societies (this thesis), and is referred to as a combined lung and diaphragm-protective ventilation approach. Today, an important barrier for implementing and evaluating such an approach is the lack of feasible, reliable and well-understood modalities to assess breathing effort at the bedside, as well as strategies for assisting and restoring respiratory muscle function during mechanical ventilation. Furthermore, monitoring breathing effort is crucial to identify potential relationships between patient management and detrimental respiratory (muscle) function that can be targeted to improve clinical outcomes. In this thesis we identified and improved monitoring modalities for the diaphragm (Part I), we investigated the impact of mechanical ventilation on the respiratory pump, especially the diaphragm (Part II), and we evaluated a novel strategy for maintaining expiratory muscle activity under mechanical ventilation (Part III)

Setting positive end-expiratory pressure:The use of esophageal pressure measurements

Purpose of reviewTo summarize the key concepts, physiological rationale and clinical evidence for titrating positive end-expiratory pressure (PEEP) using transpulmonary pressure (PL) derived from esophageal manometry, and describe considerations to facilitate bedside implementation.Recent findingsThe goal of an esophageal pressure-based PEEP setting is to have sufficient PLat end-expiration to keep (part of) the lung open at the end of expiration. Although randomized studies (EPVent-1 and EPVent-2) have not yet proven a clinical benefit of this approach, a recent posthoc analysis of EPVent-2 revealed a potential benefit in patients with lower APACHE II score and when PEEP setting resulted in end-expiratory PLvalues close to 0 ± 2 cmH2O instead of higher or more negative values. Technological advances have made esophageal pressure monitoring easier to implement at the bedside, but challenges regarding obtaining reliable measurements should be acknowledged.SummaryEsophageal pressure monitoring has the potential to individualize the PEEP settings. Future studies are needed to evaluate the clinical benefit of such approach.</p

Setting positive end-expiratory pressure:The use of esophageal pressure measurements

Purpose of reviewTo summarize the key concepts, physiological rationale and clinical evidence for titrating positive end-expiratory pressure (PEEP) using transpulmonary pressure (PL) derived from esophageal manometry, and describe considerations to facilitate bedside implementation.Recent findingsThe goal of an esophageal pressure-based PEEP setting is to have sufficient PLat end-expiration to keep (part of) the lung open at the end of expiration. Although randomized studies (EPVent-1 and EPVent-2) have not yet proven a clinical benefit of this approach, a recent posthoc analysis of EPVent-2 revealed a potential benefit in patients with lower APACHE II score and when PEEP setting resulted in end-expiratory PLvalues close to 0 ± 2 cmH2O instead of higher or more negative values. Technological advances have made esophageal pressure monitoring easier to implement at the bedside, but challenges regarding obtaining reliable measurements should be acknowledged.SummaryEsophageal pressure monitoring has the potential to individualize the PEEP settings. Future studies are needed to evaluate the clinical benefit of such approach.</p

Improved filtering methods to suppress cardiovascular contamination in electrical impedance tomography recordings

Objective. Electrical impedance tomography (EIT) produces clinical useful visualization of the distribution of ventilation inside the lungs. The accuracy of EIT-derived parameters can be compromised by the cardiovascular signal. Removal of these artefacts is challenging due to spectral overlapping of the ventilatory and cardiovascular signal components and their time-varying frequencies. We designed and evaluated advanced filtering techniques and hypothesized that these would outperform traditional low-pass filters. Approach. Three filter techniques were developed and compared against traditional low-pass filtering: multiple digital notch filtering (MDN), empirical mode decomposition (EMD) and the maximal overlap discrete wavelet transform (MODWT). The performance of the filtering techniques was evaluated (1) in the time domain (2) in the frequency domain (3) by visual inspection. We evaluated the performance using simulated contaminated EIT data and data from 15 adult and neonatal intensive care unit patients. Main result. Each filter technique exhibited varying degrees of effectiveness and limitations. Quality measures in the time domain showed the best performance for MDN filtering. The signal to noise ratio was best for DLP, but at the cost of a high relative and removal error. MDN outbalanced the performance resulting in a good SNR with a low relative and removal error. MDN, EMD and MODWT performed similar in the frequency domain and were successful in removing the high frequency components of the data. Significance. Advanced filtering techniques have benefits compared to traditional filters but are not always better. MDN filtering outperformed EMD and MODWT regarding quality measures in the time domain. This study emphasizes the need for careful consideration when choosing a filtering approach, depending on the dataset and the clinical/research question.</p

Lung Recruitment Assessed by Electrical Impedance Tomography (RECRUIT):A Multicenter Study of COVID-19 Acute Respiratory Distress Syndrome

Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. Methods: This is the analysis of patients with coronavirus disease (COVID-19) from an ongoing multicenter prospective physiological study including patients with moderate-severe acute respiratory distress syndrome of different causes. EIT, ventilator data, hemodynamics, and arterial blood gases were obtained during PEEP titration maneuvers. EIT-based optimal PEEP was defined as the crossing point of the overdistension and collapse curves during a decremental PEEP trial. Recruitability was defined as the amount of modifiable collapse when increasing PEEP from 6 to 24 cm H2O (DCollapse24–6). Patients were classified as low, medium, or high recruiters on the basis of tertiles of DCollapse24–6. Measurements and Main Results: In 108 patients with COVID-19, recruitability varied from 0.3% to 66.9% and was unrelated to acute respiratory distress syndrome severity. Median EIT-based PEEP differed between groups: 10 versus 13.5 versus 15.5 cm H2O for low versus medium versus high recruitability (P, 0.05). This approach assigned a different PEEP level from the highest compliance approach in 81% of patients. The protocol was well tolerated; in four patients, the PEEP level did not reach 24 cm H2O because of hemodynamic instability. Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension.</p

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